Penicillin is a major medical advancement, known for combating bacterial infections. Discovered from Penicillium molds, it was one of the first effective treatments against many bacterial pathogens, including staphylococci and streptococci. Its introduction transformed infectious disease treatment, providing a powerful tool against previously life-threatening conditions.
The Bacterial Cell Wall
Bacteria possess an outer layer called the cell wall, distinct from human cells. This structure provides essential support, maintaining the bacterium’s shape and protecting it from external forces. The primary component of the bacterial cell wall is peptidoglycan. It forms a mesh-like scaffold around the bacterial cytoplasmic membrane, acting as a protective enclosure.
The peptidoglycan layer consists of linear chains made of two alternating sugar derivatives: N-acetylglucosamine (GlcNAc or NAG) and N-acetylmuramic acid (MurNAc or NAM). These sugar chains are cross-linked by short peptide chains, typically containing four or five amino acid residues. This network of sugars and peptides creates a strong, rigid structure that allows the bacterial cell to withstand internal pressure. The thickness of this peptidoglycan layer varies between different types of bacteria, with Gram-positive bacteria having a significantly thicker layer compared to Gram-negative bacteria.
Penicillin’s Targeted Action
Penicillin belongs to a class of antibiotics called beta-lactams, characterized by a four-membered beta-lactam ring structure. Penicillin interferes with bacterial growth by interacting with enzymes essential for cell wall construction. During bacterial cell wall synthesis, new peptidoglycan units are added and connected to the existing structure.
A key step in this process is the formation of cross-links between peptidoglycan strands, catalyzed by enzymes known as transpeptidases. These transpeptidases are also called penicillin-binding proteins (PBPs) due to their affinity for penicillin. Penicillin mimics the natural substrates these enzymes normally bind. The beta-lactam ring of penicillin binds irreversibly to the active site of PBPs, forming a stable complex.
This binding event inactivates the transpeptidase enzymes, preventing them from performing their cross-linking function. Without proper cross-linking, newly synthesized peptidoglycan units cannot be integrated effectively into the growing cell wall. This inhibition specifically targets the final stages of peptidoglycan synthesis, leading to the construction of a defective and unstable cell wall.
Why Bacteria Die
Disrupting cell wall synthesis has severe consequences for bacteria. The weakened wall can no longer provide adequate rigidity or support to the bacterium.
Bacteria typically exist in environments where the concentration of solutes inside their cytoplasm is higher than outside, creating a natural osmotic pressure that pushes water into the cell. Normally, the intact cell wall counteracts this internal pressure, preventing the cell from swelling excessively. However, with a defective cell wall, the bacterium loses its ability to resist the influx of water. Water rushes into the cell, causing the cell to expand beyond its capacity, leading to osmotic lysis where the bacterial cell membrane ruptures and the cell contents spill out, resulting in bacterial death.